There is no small-diameter vascular prosthesis that is capable of emulating the biologic and physical properties of the normal arterial wall. The goal of this proposal is to develop a small-diameter prosthetic vascular graft using nanofiber technology. Our hypothesis is creating a nanofibrous vascular graft by electrospinning an ionic polyurethane will result in a graft that possesses properties similar to that of native artery. The potent anti-thrombin agent recombinant hirudin (rHir) will be covalently bound to functional groups within the polymer, resulting in an anti-thrombotic surface. The elastic properties of the ionic polymer will provide circumferential compliance, with longitudinal stretch and kink- resistance prevented by a thin braided Dacron mesh within the graft wall. The specific objectives are to: 1) optimize electrospinning methodology, 2) develop a Dacron inner-wall reinforcement, 3) electrospin PEU grafts containing reinforcement, 4) characterize physical and chemical properties, 5) covalently link rHir to PEU grafts, 6) characterize surface antithrombin properties, 7) evaluate blood interaction with grafts and 80 assess surface rHir stability under simulated arterial flow conditions. Phase II of this project will evaluate these PEU grafts in a canine carotid artery model. Development of a bioactive small-diameter vascular graft would have a significant impact on small vessel repair and replacement. PROPOSED COMMERCIAL APPLICATIONS: Development of a bioactive small-diameter vascular graft would have a significant impact on small vessel repair and replacement. These grafts could be utilized in peripheral bypass as well as for coronary artery bypass, which have some 500,000 grafts are implanted annually in the United States. For example, the potential annual market value for an "off-the-shelf" synthetic coronary artery bypass graft could exceed $1.5 billion.